EFFECTS OF A NOVEL, LOW-MOLECULAR-WEIGHT INHIBITOR OF LIPID-PEROXIDATION ON ISCHEMIA-REPERFUSION INJURY IN ISOLATED RAT HEARTS AND IN CULTURED CARDIOMYOCYTES

We investigated the effect of H290/51, a novel, low-molecular-weight i nhibitor of lipid peroxidation, on cardiac ischemia-reperfusion injury . Lactate dehydrogenase (LD) release from cultured cardiomyocytes expo sed to 1 h hypoxia and 4 h reoxygenation was measured after pretreatme nt with different concentrations of H290/51. In another series, Langen dorff-perfused rat hearts were exposed to 30 min global ischemia and 6 0 min reperfusion (n = minimum 10 in each group): 1. Control ischemia- reperfusion. 2. Vehicle throughout the experiment. 3, Vehicle during s tabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/5 1 throughout the experiments. During reoxygenation of isolated cardiom yocytes, H290/51 dose dependently inhibited LD release with an pIC(50) value of 7.2. +/- 0.4 (mean +/- SEM), with 10(-6) mol/l as the lowest efficient concentration. In isolated hearts ischemia-reperfusion indu ced severe reperfusion arrhythmias, reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and increased LV end-diastoli c pressure (LVEDP). LD activity in the effluent increased. H290/51 thr oughout perfusion (group 4) reduced the occurrence of seven reperfusio n arrhythmias (p <.0001), attenuated the decrease of LVDP (p < .008), and CF (p <.006), the increase of LVEDP (p <.008), and the release of LD (p <.002). Tissue contents of thiobarbituric acid-reactive substanc es did not increase during reperfusion in controls, but was reduced in group 4 (p < .004). H290/51 given only during nperfusion (group 3) te nded to improve cardiac function, but significantly so only for increa se of CF (p <.01). The lipid peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia-reperfusion. (C) 1998 Elsevier Sci ence Inc.